Bulletin europeen de physiopathologie respiratoire最新文献

Almitrine bismesylate (A) is a peripheral chemoreceptor agonist that increases ventilation, improves V/Q matching, increases PaO2 and decreases PaCO2 in patients with COPD. We have used a placebo-controlled double-blind cross-over study to compare the effect of 1.5 mg.kg-1 A and placebo (P) (given orally twice a day for 14 days with a 2 wk wash-out period between) on sleep quality, blood oxygenation during sleep and the ventilatory response to hypoxia and hypercapnia when awake. We have measured ear oxygen saturation (SaO2) and EEG sleep stages during nocturnal sleep in 13 patients with COPD (FEV1 0.94 +/- 0.31 1). When awake and during P period PaO2 was 51.4 +/- 10.7 mmHg (SD), PaCO2 53.1 +/- 7.1 mmHg and SaO2: 83.1 +/- 8.0%: during A treatment PaO2 increased to 55.8 +/- 7.8 mmHg (p less than 0.01 paired Wilcoxon test), PaCO2 decreased to 48.5 +/- 6.4 mmHg (p less than 0.05) and SaO2 increased to 86.9 +/- 2.6 (p less than 0.01). A reduced nocturnal hypoxaemia: 1) during P treatment mean stage I SaO2 was 73.2 +/- 13.2%, stage II 70.5 +/- 15.7%, stage III 66.5 +/- 18.5%, stage IV 73.3 +/- 12.7% and rapid eye movement (REM) sleep 59.2 +/- 14.8%; the corresponding SaO2 values during A treatment were higher: stage I SaO2 80.6 +/- 5.2% (p less than 0.05), II 78.6 +/- 6.2% (p less than 0.01), III 77.3 +/- 7.4% (p less than 0.01), IV 80.4 +/- 3.8% (p less than 0.05), REM 69.9 +/- 7.9% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic alveolar hypoxia whether due to living at high altitude or to lung disorders, such as chronic obstructive lung disease (COLD), leads to development of pulmonary arterial hypertension (PAH). Sustained PAH is the principal cause of right ventricular hypertrophy (RVH) and failure. The majority of high altitude residents, in spite of having moderate PAH and hypoxemia with some degree of RVH, manage to live actively and productively through acclimatization. Although the processes of acclimatization decrease the magnitude of oxygen (O2) pressure drop at each step of the O2 tension cascade, O2 pressures in the tissue capillaries and mixed venous blood are lower than those at sea level. Since the cardiac output and O2 consumption in residents at high altitude have been shown to be comparable to those of sea level residents, the importance of adaptive changes at the tissue level to facilitate diffusion and utilization of O2 must be emphasized. In patients with COLD and hypoxaemia, most of the adaptive changes that have been shown to operate in high altitude residents do not occur, or have not been observed consistently. At present, only long-term O2 therapy has been shown to improve survival and lower pulmonary artery pressure (Ppa), but the changes of the latter are generally too modest to explain the former. It may be that the improved survival is mainly achieved by correcting hypoxaemia, thereby improving tissue oxygenation, rather than lowering Ppa.

Peripheral nervous system alterations during chronic obstructive airways disease (COAD) with respiratory insufficiency seem more frequent than usual neurological practice would suggest. Almost a third of COAD patients have clinical evidence of peripheral neuropathy and two thirds have electrophysiological abnormalities. The presentation consists of a polyneuropathy often subclinical or with predominantly sensory signs, which has the neurophysiological and pathological features of predominantly axonal neuropathy. The presumed etiopathogenic factors are multiple: chronic hypoxia, tobacco smoke (which contains at least three neurotoxic constituents) alcoholism, malnutrition and adverse effects of certain drugs. Hypoxia probably plays the leading part, either by direct action on nerves fibres or by enhancing the effects of other neurotoxic factors or deficiencies.

Sleep hypoxaemia was investigated in 11 patients. The patients were randomly assorted to receive almitrine bismesylate therapy or identical placebo tablets. Almitrine therapy was associated with an increase of daytime PaO2, mean SaO2 awake and during sleep, and less time when SaO2 fell below 90% during sleep. The number of desaturation episodes and lowest SaO2 were unaffected.

701 patients, age 61.9 +/- 8.3 yr (mean +/- SD), with hypoxaemic chronic obstructive airways disease (COAD) were entered into a one yr placebo-controlled double-blind study to determine the effect of oral almitrine bismesylate on arterial blood gas tensions and clinical condition. Initial arterial O2 tension (PaO2) was 7.6 +/- 0.8 kPa (57.0 +/- 6.2 mmHg) and arterial CO2 tension (PaCO2) was 6.0 +/- 0.9 kPa (45.2 +/- 6.7 mmHg). Forced expiratory volume in one second (FEV1) was 0.87 +/- 0.35 l and forced vital capacity (FVC) was 2.31 +/- 0.72 l. 163 patients, evenly distributed between treated and untreated groups, were receiving long-term O2 therapy; other conventional therapy was continued. In a stabilization period before treatment, excellent reproducibility of blood gas tensions and spirometry was achieved. In the placebo group (P; n = 357), little change in physiological measurements or clinical assessment was recorded, 90 patients (25%) were lost from the study, mostly due to deterioration of their respiratory disease or to death; 3.4% withdrew for adverse reactions. The almitrine group (A; n = 344), received 100-200 mg per day orally in two divided doses, depending on the improvement in PaO2 achieved. On entry to the study their blood gas tensions, lung function tests, clinical assessment, history of hospitalization and frequency of right heart failure were not significantly different from the placebo group. After one yr of treatment, PaO2 rose from 7.6 +/- 0.8 kPa (57.4 +/- 6.1 mmHg) to 8.5 +/- 1.3 kPa (63.7 +/- 9.7 mmHg), p less than 0.001 compared with the placebo group. Red cell count decreased p less than 0.001 compared with the placebo group and FEV1 increased from 0.92 l to 0.95 l, p less than 0.001 compared with the placebo group. Dyspnoea, assessed on a 100 mm analog scale was unchanged in the almitrine group as a whole, but some individual patients withdrew on account of breathlessness. A smaller proportion of patients in group A were hospitalized and had episodes of right heart failure during the study than in group P (p less than 0.05). Vital signs, biochemistry and ECG characteristics did not change. 139 patients (40%) in this group did not complete the study, 35 (10%) through deterioration of respiratory symptoms or death (4.9%); 43 (12.5%) withdrew because of adverse reactions, either drug-related or not. The most frequent adverse reactions were gastro-intestinal, central nervous system disturbances, increased dyspnoea and peripheral paraesthesiae.(ABSTRACT TRUNCATED AT 400 WORDS)

Almitrine bismesylate has been thought to provoke peripheral neuropathies in patients with chronic obstructive pulmonary disease (COPD). However, there seems to exist alterations of peripheral nerve function in patients with COPD, who have not taken almitrine. We have therefore examined 22 patients with COPD and no other cause of peripheral neuropathy (PN), before and after 6 and 12 months of treatment with almitrine (50 mg bd). Seventy-eight similar patients, who did not take almitrine, were also studied (controls). Sixty-four per cent of controls, and 55% of almitrine patients initially had at least one neurophysiological abnormality. There was no change in the studied parameters after 6 months and one year's treatment with almitrine.

The role of the carotid body in the ventilatory changes of exercise is reviewed. Peripheral chemoreceptor function was studied in 20 patients with chronic airways obstruction. The patients were treated double-blind and randomly allocated to placebo and almitrine bismesylate 50 mg b.d. before undertaking an exercise programme at day 0 and after 30 and 60 days of therapy. Patients on almitrine therapy had an improved resting arterial oxygen tension (PaO2) which was maintained during exercise. A statistically significant improvement of effort tolerance was observed after 60 days treatment with almitrine.